Search PubMed⌕ Search

Biomedical subjects

M M Hansen

Publications and source records attributed to M M Hansen.

At least 73 records · Page 4Linked to original sources

Simultaneous presence of translocations t(14;18) and t(2;8) in a case of chronic lymphocytic leukemia.

We report a patient with classical chronic lymphocytic leukemia of IgM kappa phenotype and a stable clinical course, in which repeated chromosome analyses of blood lymphocytes revealed the coexistence of t(14;18), a marker often associated with follicular low grade lymphocytic lymphomas, and t(2;8), a variant of the t(8;14) typically seen in Burkitt's lymphoma. Both these translocations involve immunoglobulin gene regions, the t(2;8) being almost always found in patients with kappa light chain restriction. However, in an EBV-immortalized cell line of this patient, most karyotypes contained t(14;18) alone, without the t(2;8). This suggests that t(14;18) was the primary cytogenetic event, and that t(2;8) evolved subsequently. As a secondary cytogenetic event, the t(2;8) may not share the grave clinical consequences of a primary t(2;8) as seen in Burkitt's lymphoma and related disorders.

Aged↗

The bone marrow histological pattern has independent prognostic value in early stage chronic lymphocytic leukaemia.

The initial diagnostic bone marrow specimens from 90 consecutive, untreated patients with chronic lymphocytic leukaemia were examined for the pattern of lymphocytic infiltration in relation to clinical stage (International Workshop System) and survival. Three non-diffuse (interstitial, nodular, mixed nodular-interstitial) and one diffuse pattern were recognized. Generally, the bone marrow patterns correlated well with clinical stage: a non-diffuse pattern prevailed in early, and a diffuse pattern in later stages. However, with a Cox analysis of the covariate effect of clinical stage and bone marrow pattern on survival, the bone marrow pattern was shown to have independent prognostic significance in the early stage A in which a diffuse pattern carried a fourfold increase in death rate as compared to a non-diffuse pattern. These high risk patients could not be identified by the Rai substages of the International Workshop System.

Aged↗

Cefotaxime monotherapy in septicemic patients with hematological malignancies.

Cefotaxime at a dosage of 3 gm intravenously every eight hours was administered to 80 patients with hematological malignancies and suspected septicemia. Blood samples for culturing were taken before and during antibiotic therapy. Nineteen patients had verified bacteremia and ten of them responded completely to cefotaxime. Twelve of the 19 patients had granulocyte counts of less than 0.5 X 10(9)/L. Minimal inhibitory concentrations of cefotaxime, ceftazidime, moxalactam, cefsulodin, cefoxitin, cefuroxime, and cefamandole against the pathogens were measured: cefotaxime was the best cephalosporin against gram-negative isolates and was found acceptable against gram-positive bacteria. In 61 patients no bacteremia could be demonstrated, but specific pathogens were isolated in 11 patients: from the urine in five, from the sputum in five, and from a perianal abscess in one. Complete response was obtained with cefotaxime in seven of these 11 patients. Monotherapy with cefotaxime in septicemic patients with hematological malignancies appears to be a valuable alternative to other antibiotic regimens.

Aged↗

Testicular function in young men in long-term remission after treatment for the early stages of Hodgkin's disease.

16 young men in long-term remission after standard treatment for the early stages of Hodgkin's disease were examined for testicular function 48 to 125 months after termination of therapy. The patients had received mantle field irradiation, plus either irradiation of infradiaphragmatic lymph nodes (7 patients) or 6 cycles of MOPP (9 patients). 5 patients had almost normal semen quality judged by seminal fluid analysis. 11 patients had reduced semen quality (8 severely reduced) and often elevated FSH values. Semen samples of poor quality were significantly more common in patients treated with MOPP (7/9) than in those treated with infradiaphragmatic irradiation (1/7). One patient showed signs of regeneration of spermatogenesis. None had experienced reduction in libido and sexual performance after therapy; correspondingly, none had below normal testosterone values or elevated LH values. Patients should be informed about the risk of infertility before treatment. If in a given case several treatment options with equal prospective antineoplastic effect are weighed against one another, the patient's possible desire to retain fertility should favour the use of radiotherapy as opposed to chemotherapy, especially including alkylating agents.

Adult↗

Ovarian function in young women in long-term remission after treatment for Hodgkin's disease stage I or II.

16 young women in long-term remission after first-line treatment for the early stages of Hodgkin's disease were examined for ovarian function 48 to 125 months after termination of therapy. The patients had received mantle field irradiation, plus either irradiation of infradiaphragmatic lymph nodes or 6 cycles of MOPP. 4 patients showed signs of ovarian failure judged by menopausal symptoms, menstrual pattern and/or hormone values. 12 patients had functioning ovaries; 8 of these had become pregnant after treatment, 2 had had an induced abortion, and 7 had given birth to a total of 9 healthy babies after treatment. The patients with signs of ovarian failure were older than the others, but the difference was not statistically significant. No difference between the patients who had received different treatments was established, nor does the study confirm the proposed protective effect of oral contraceptives. For women under 35 years of age, the long-term chances of preserving ovarian function after standard treatment for the lower stages of Hodgkin's disease seem to be much better than hitherto assumed.

Adolescent↗

A randomized study of radiotherapy versus radiotherapy plus chemotherapy in stage I-II non-Hodgkin's lymphomas.

In a randomized, prospective trial from 1974-1978, 73 patients with non-Hodgkin's lymphomas in clinical Stage I or II were treated with extended field radiotherapy alone (RT) or RT plus adjuvant chemotherapy with vincristine, streptonigrin, cyclophosphamide and prednisone (RT + CT). With a median follow-up time of five years, 54% have relapsed in the RT group versus only 10% in the RT + CT group (P less than 0.01). There is no statistical difference in the overall survival yet, but 13/14 deaths in the RT group versus only 3/12 in the RT + CT group were due to progressive disease. Among patients with unfavorable histology, 13/22 in the RT group have died from disease progression against 3/34 in the RT + CT group (P less than 0.01). The results are in agreement with those from two other series published in detail. Based on these results we therefore recommend to use adjuvant CT with RT in all Stage I-II patients with unfavorable histology. Further observation is necessary before a conclusion can be drawn for the lymphoma patients with more favorable histology.

Antineoplastic Agents↗

Cefotaxime versus ampicillin, methicillin and netilmicin in combination for treatment of febrile episodes in patients with haematologic malignancy.

A prospective, randomized trial comparing treatment of 61 febrile episodes with cefotaxime (CTX) versus a combination of ampicillin, methicillin, and netilmicin (AMN) was carried out in 58 patients with leukaemia or malignant lymphoma, of whom 28 had a granulocyte count of less than or equal to 500 X 10(6)/l. The overall response frequency was 63% for CTX against 49% for the AMN combination, the latter figure being lower than generally reported in the literature. The difference was not statistically significant. In 21 episodes pathogens were isolated, 16 of them from the blood. All isolated bacteria but one, a strain of Bacteroides fragilis, were fully sensitive to at least one of the three antibiotics in the combination, and all but one, a strain of Listeria monocytogenes, were fully sensitive to CTX. These results indicate that CTX seems to be a promising alternative as monotherapy for empiric treatment of febrile episodes in patients with haematologic malignancies. Further investigations will, however, be required before completely rational choices between mono and combination therapy of febrile episodes in immunosuppressed patients can be made.

Adolescent↗

Nuclear clefts in chronic lymphocytic leukaemia. A light microscopic and ultrastructural study of a new prognostic parameter.

Peripheral blood lymphocytes from 48 consecutive, newly diagnosed CLL patients were examined by light- and electron-microscopy for the presence of nuclear cleaving or folding. On this basis, the patients could be subdivided into 2 easily separable morphological groups. In 42 patients the lymphocytes had regular round nuclei. In 6 patients (13%) the lymphocytes of peripheral blood had a highly irregular nuclear outline characterized by pronounced cleaving or folding of the nuclear membrane. In 4 of these 6 patients immunological investigations demonstrated membrane markers consistent with B-cell monoclonality. Age, sex, distribution between stages as well as mode of clinical presentation were all alike in the 2 groups of patients. In spite of this a statistically significant, highly increased mortality was observed in patients with lymphocyte nuclear irregularities. Thus, 50% of all deaths occurred in this small group of patients. These findings indicate that lymphocyte nuclear cleaving or folding represents a stage-independent prognostic parameter, which permits selection of a small but easily identified high-risk group of patients.

Adult↗

Chronic lymphocytic leukaemia of T cell origin. Clinical variation possibly due to involvement of different T lymphocyte subpopulations.

Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E-rosettes, have no surface-membrane-bound Ig, but Fc-receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4- and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato-splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.

Aged↗

Cytoplasmic inclusions in lymphocytes of chronic lymphocytic leukaemia. A report of 10 cases.

Peripheral blood from 90 CLL patients was examined by light-and electron-microscopy for the occurrence of crystalline inclusions in lymphocytes. Inclusions were demonstrated in 10 patients (11%). In these patients the inclusions were present in 5-45% of peripheral blood lymphocytes. In the light microscope the inclusions appeared as rectangular, unstained structures in May-Grünewald Giemsa and PAS stains. In the electron microscope the inclusions appeared as intracytoplasmic, completely partially membrane-bound bodies, which were often associated with dilated profiles of rough endoplasmic reticulum. The ultrastructure of the inclusions was granular. In immunofluorescence staining the inclusions were found to contain immunoglobulin of the same type and class as the surface membrane-bound immunoglobulin of the neoplastic lymphocytes, most frequently IgM-lambda. The lymphocytes of one case with kappa light chains at the cell surface membrane contained inclusions of the same ultrastructural morphology as those of the other cases with lambda light chains. The presence of inclusions was not associated with any specific clinical or prognostic features. the inclusions persisted during antileukaemic therapy. Their formation may be related to a dysfunction in the synthesis of surface membrane-bound immunoglobulins.

Cytoplasm↗

Fatal hepatitis following irradiation and vincristine.

The increasing use of combination therapy with irradiation and cytostatics in malignant disease increases the risk of toxicity. An account is given of a patient with liver toxicity terminating fatally, in whom increased radiosensitivity may have been induced by vincristine.

Adult↗

The applicability of simple blood and bone marrow variables in prediction of acute leukaemia in patients with acquired bi- or pancytopenia.

A retrospective study of 44 patients presenting with acquired bi- or pancytopenia (B/PC) and no evidence of any causal disorder was carried out. 12 patients developed acute non-lymphoblastic leukaemia after 2-51 months. Compared to the nonleukaemic subjects the preleukaemic patients at the onset of B/PC had significantly higher counts of myeloblasts and other myelopoietic cells in the bone marrow, more cellular marrows due to more dense cellularities of all compartments, higher blood granulocyte and monocyte counts, more pronounced anisocytosis, and in some cases a small number of circulating myeloblasts. A stepwise multiple logistic regression analysis identified 3 combinations of variables displaying significant simultaneous association with subsequent leukaemic transformation. Among these the combination of marrow myeloblast percentage and blood granulocyte count might be applicable to early prospective identification of patients with preleukaemic B/PC.

Acute Disease↗

Chronic lymphocytic leukaemia: a test of a proposed new clinical staging system.

102 patients with chronic lymphocytic leukaemia underwent clinical staging according to 2 systems: the Rai staging system with 5 stages (0: lymphocytosis, I: palpable lymph nodes, II: hepato- or splenomegaly, III: Hb below 110 g/1, IV: platelet count below 100 X 10(9)/1) was compared to a staging system recently proposed by Binet, with only 3 stages (A: not more than 2 areas of palpable nodes or organs, B: at least 3 areas, C: Hb below 10 g/1 or platelet count below 100 X 19(9)/1). With the 3-stage system statistically significant differences between the stages were obtained, whereas some of the Rai stages (I-II-III) were only poorly separated. Non-haemolytic anaemia with Hb below 100 and 110 g/1) or auto-immune haemolytic anaemia. Chest X-ray findings did not influence the clinical stage.

Anemia↗

Effect of sodium nitroprusside on hypoxic pulmonary vasoconstriction in the dog.

The objective of the study was to determine the direct actions of sodium nitroprusside (SNP) on the pulmonary vasculature actively constricted by hypoxic ventilation in the closed-chest dog. In 21 supine anesthetized (pentobarbital sodium, 25 mg/kg) dogs the left lower lobe was catheterized with a 20 F wedged-flow catheter. With constant flow to this lung lobe, lobar pulmonary artery pressure (PAP), left ventricular end-diastolic pressure (LVEDP), and lobar pulmonary vascular resistance (PVR) were studied during room air and 10% O2 mechanical ventilation. With lobar flow and LVEDP constant, observed changes of lobar PAP and PVR represent direct effects on vascular tone unaffected by passive factors. Ventilation with 10% O2 resulted in a significant increase in lobar PAP [12.2 +/- 1.6 to 17.2 +/- 1.2 (SE) Torr] and PVR [42.2 +/- 13.3 to 61.2 +/- 15.0 (SE) Torr X 1(-1) X min]. Then during continued hypoxia in 12 animals, femoral vein infusion of SNP at doses of 1, 2, and 5 microgram X kg-1 X min-1 resulted in significant decreases in lobar PAP to 14.8 +/- 1.5, 14.8 +/- 1.5, and 13.4 +/- 1.6 Torr, respectively, and in PVR to 56.7 +/- 14.1, 54.0 +/- 13.9, and 47.8 %/- 13.2 Torr X 1(-1) X min, respectively. In six animals the sequence of drug infusion was then reversed with similar results. It is concluded that the actively constricted pulmonary vascular bed is directly dilated by SNP infusion.

Animals↗